Compound of gall acids and process of making same



Patented July 17, 1928.

UNITED STATES PATENT OFFICE."

ALPHONSE GAIS AND PAUL SCHEIDEGGEB, OF BASEL, SWITZERLAND, ASSIGNOBB TO I THE FIRM SOCIETY OF CHEIICAL INDUSTRY IN BASLE, OF BASEL, SWITZERLAND.

GOIPOUND OF GAIL ACIDS AND PBOCI ISS'DF MAKING SAIE.

No Drawing. Application filed July 31, 1926; Serial No. 126,385, and in Switzerland September 2, 1825.

6 Recent researches have shown that the formation of concretions in the, gall is to be ascribed to a deficiency of protective colloids which are able to keep in colloidal solution the cholesterin and other constitu- 10 ents of the gall, for instance the calcium bilirubinate.

. Based upon these researches attempts have been made to supply the said deficiency by ingestion. of protective colloids, such as lecithin or compounds thereof, with gall acids.

According to the present invention new compounds are obtained with aid of which the described object can be attained in an advantageous manner, by causing the acids of the gall to react with acylated diamines instead of with lecithin, asymmetrically acylated diamines being preferably used.

The asymmetrically acylated diamines D not only have an essentially stronger emulsifying capacity than lecithin has, but also have an additional therapeutic action which is highly desirable for the purpose in question and is not to be found in lecithin.

That is tov say they have on the one hand a ver strong effect in inducing the flow of gall: which effect is equal to that of the most active gall acids, andv on the other hand a pronounced antiseptic action.

The asymmetrically acylated diamines give well characterized compounds with the gall acids.

By the term ular carboxylic acids contained in the gall,

40 or their products of partial anhydrization,

oxidation, etc., are understood. The empirical formula of the more important ga acids is the following Cholic acid C,,H ,O,.COOH Desox cholic acid C H ,O .COOH Dehy rocholic acid C ,,H O CO0H Apocholic acid C H ,O,.COOH

The reaction between the gall acid and the acylated diamine occurs according to the laws of the salt formation. Thus for instance, the formation of the dehydrochogall acids the high moleclate of oleyl-di'cthyletliylene-diamine may be lllustrated by the equation:

. 7 7 211: CflHl'Ol-COOH CnHnCO-NHCHzCHaN Call:

The compounds in question may be obtained by supply bringing together the acylated diamine and the gall acid, it may be in presence or absence of asolvent; for instance a solution of the components may be evaporated or the components may be triturated together 'or' fused together, or analogously treated. I The new compounds are generally crystalline bodies which dissolve easily in methyl alcohol, ethyl alcohol, chloroform or acetone; partly they are dissolved with somewhat greater difliculty in ether.

'lllhey are applicable in disorders of the 0'3, i

he following examples illustrate the invention:-

Ewample 1.Dehyd-rocholate of oleyldiethyZethg Zenediamine.

.. (31H! Molecular proportions of dehydrocholic .acid and oleyldiethylethylenediamine are Example $2.-O'holate of isovaZem Z-diethg L ethg lenedia'lm'ne.

V Calla CgH O COOH.C4H C0NHCH|CH|N Cal-l;

This compound, obtained from cholic acid and isovaleryl-diethylethylenediamine 65 C. and melts at 90C.

in the manner described in Example 1, is a white crystalline powder which sinters at Eim'mple 3.-0'Irolate of be nzoyldiethylethylenedianmma.

' Calla CuHnO QO0ILC5H5CONHCHzCHzN CzH An alcoholic solution of molecular proportions of ch'olicacid and benzoyldiethylethylenediamine is gradually evaporated. The compound produced is a white crystalline powder which softens above 70 C. and 1s molten at 99 C.

Example 4.--0'b0late of stearyld'iethyl- This compound is obtained in the manner described in Example 3 from molecular proportions of cholic acid and stearyldiethylethylenediamine. "It forms colourless, fine needles, melting at 67 C.

Example 5. Desoa: 1 elwlate of steam Z11 1:- why ethylenediamine v I v CuHuUz'COOH.CnHuCONHCHzCHzN Call;

The compound obtained from molecular proportions of desoxycholic acid and stearyldiethylethylenediamine in the manner des ribed in Example 1 forms small coloigless, soft flat prisms which melt at 58 Example 6.-Ap0'cholate of stearyldiethylethylenediamine.

01H CgHuOzCOOH.CuHuCONHCHaCHaN I IHl Ernample 7.Dehydrochozic acid of diethylamimethg Zearboma/ic acid-menthylestar.

- Calla CuHuOaCOOHQmHnO CONHCIhCHaN Molecular proportions of dehydrocholie acid and diethyla-minoethylcarbamic acidmenthylester are dissolved-in methyl alcohcy'lated diamines with gall acids hol and. the solution evaporated. The compound is a hard crystalline mass which begins to soften at 188 C. and is clearly molten at 199 C.

.\.-l ehg droeholate of stearyl- Ewam pie I et/q Zewedia In/ine.

I CgllagOgCOO [1.(17lluCONlLUllaCHl-NH:

This compound is obtained from molecular proportions of dehydrocholic acid and stearylethylcueiliamine in .the manner decribed in Example 7. 1t is a crystalline mass which sinters at 110"v C. and is clearly molten at about 133 C.

What we claim is 1. Process for the manufacture of compounds of gall acids by causing an acylated aliphatic diamine to react with a gall acid.

2. Process for the manufacture of compounds of gall acids by causing an acylated aliphatic diamine to react with a gall acid in presence of a solvent.

3. Process for the manufacture of compounds of gall acids by causing an asymmetrically acylatcd aliphatic diamine to react with a gall acid.

4. Process for the manufacture of compounds of gall acids by causing an asymmetrically acylated aliphatic diamine to react with a gall acid in presence ofa solvent.

5. Process for the manufacture of compounds of gall acids by causing an asymmetrically acylated aliphatic diamine to react with deh'ydrocholic acid.

6. Process for the manufacture of compounds of gall acids by causing an asymmetrically acylated aliphatic diamine to react with dehydrocholic acid in presence of a solvent.-

7. Process for the manufacture of compounds of gall acids by causing oleyldiethylethylenediamine to react with a gall acid.

8. Process for the manufacture of compounds of gall acids by causing oleyldiethylethylenediamine to react with a gall acid in presence of a solvent.

9. Process for the manufacture of dehydrocholate of oleyldiethylethylenediamine by causing oleyldiethylethylenediamine to react with dehydrocholic acid.

10. Process for the manufacture of dehydrocholate of oleyldiethylethylenediamine by causing oleyldiethylethylenediamine to react with dehydrocholic acid in presence of a solvent.

' 11. Asnew products the com ounds of ing well characterized generally crystalline bodies, which dissolve easily in methylalcohol, ethylalcohol, chloroform or acetone.

12. As new products the compounds of asymmetrically acylated diamines with gallacids being well. characterized generally crystalline bodies, which dissolve easily in methylalcohol, ethylalcohol, chloroform or acetone.

13. As new products the compounds of asymmetrically ac lated diamines with dehydrocholic acid ing well characterized generally crystalline bodies, which dissolve easily in methylalcohol, ethylalcohol', chloroform or acetone.

14. As new products the compounds of oleyldiethylethylenediamine with gall acids being Well characterized generally crystalline bodies, which dissolve easily in methylalcohol, ethylalcohol, chloroform or acetone.

crystalline masseasily soluble in methylalcohol, ethylalcohol, chlorofroin and acetone becoming brown at'150'C. and being fully molten at 200 C.

In witness whereof we have hereunto signed our names this, 16th day of July, 1926. ALPHONSE GAMS.

PAUL SCHEIDEGGER. 

